A study led by Chunxiao Song (Ludwig Institute for Cancer Research) and Shivan Sivakumar (Department of Oncology and Oxford University Hospitals Foundation NHS Trust) optimised the TAPS technology developed in Chunxiao’s lab for the mapping of DNA methylation for use on cell-free DNA (cfDNA). Such circulating cfDNA, a tiny proportion of which is shed by tumours in people with cancer, is the focus of efforts to develop liquid biopsies for early cancer detection, most of which have focused on the detection of mutations. Knowing the methylation state of cfDNA can, however, provide critical information unavailable in the DNA sequence alone, such as the likely location of a tumour.
The researchers reported in a paper in Science Advances their use of the optimised TAPS—named cfTAPS—on 85 samples from patients with hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC) and noncancer controls, showing that they could generate the most comprehensive cfDNA methylome to date using just 10 nanograms of cfDNA. They demonstrated that cfTAPS provides multimodal information about cfDNA, including its methylation patterns, the tissue from which it originated and DNA fragmentation. The integrated analysis of these epigenetic and genetic features enabled accurate identification of early HCC and PDAC.